The Markey Cancer Center (MCC) Protocol Review and Monitoring System (PRMS) provides thorough review of clinical trials for scientific validity, feasibility and prioritization within the clinical trials portfolio and monitoring of scientific progress. The PRMS must approve all interventional cancer research prior to study initiation and has the authority to recommend closure of trials for lack of scientific progress or patient accrual. The PRMS provides a framework which aims to balance appropriate resource utilization while maximizing the opportunities for current and future patients with cancer in this region to participate in clinical trials, including the underserved area of Appalachian Kentucky. The development of novel MCC investigator-initiated clinical trials and participation in high-priority national trials provide a robust portfolio of therapeutic research studies available to MCC patients.